An integrated numerical and experimental framework for modeling of CTB and GD1b ganglioside binding kinetics

A mathematical model is developed and validated for a multistep binding process between cholera toxin subunit B (CTB) and GD1b receptors that precedes cholera infection. To study the dynamics of the complex CTB‐GD1b binding mechanisms, cooperative binding effect and GD1b receptor aggregation in the host cell membrane are considered. More reliable parameters for the CTB‐GD1b binding kinetics are estimated by quantitatively calibrating the proposed multistep binding model against the experimental measurements obtained from the novel nanocube‐based biosensor. Specifically, a numerical scheme that includes the sensitivity analysis, parameter estimation and dynamic optimization is implemented for the model calibration. Through this scheme, identifiable model parameters are determined. After those selected parameters are estimated, the calibrated model and the experimental measurements were in reasonable agreement for different CTB and GD1b concentrations, which shows a promising approach for identification of the kinetics of CTB binding to the host cell membrane.